Method for detecting potential cellular toxicity of compounds

G - Physics – 01 – N

Patent

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G01N 33/50 (2006.01)

Patent

CA 2333115

The subject invention involves a test procedure for screening for potential cellular toxicity of a test compound comprising the following steps: a) making liposomes from one or a mixture of lipids to simulate a cell membrane composition of interest, the liposomes being made in an aqueous medium having a pH which is thereby the inside pH of the liposomes; b) incorporating the liposomes in an aqueous test medium having a pH at least about 0.5 pH units above the inside pH of the liposomes, whereby a pH gradient exists between the test medium and the insides of the liposomes; c) incorporating a fluorescent dye in the test medium, the dye having a tendency to penetrate into the liposomes due to the pH gradient, the dye being pH sensitive such that the fluorescence of the dye is quenched inside the liposomes; d) incorporating the test compound in the test medium; whereby, if the test compound disrupts the structure of the liposomes or otherwise causes dissipation of the pH gradient between the test medium and the insides of the liposomes, the fluorescence of the dye is not quenched; e) determining the fluorescence of the test medium and comparing the determination with those of controls.

L'invention concerne une procédure d'essai pour le criblage de la toxicité cellulaire potentielle d'un composé d'essai, comprenant les étapes suivantes: (a) fabrication de liposomes à partir d'un mélange de lipides, pour la simulation d'une composition de membrane cellulaire à analyser, les liposomes étant fabriqués dans un milieu aqueux ayant un pH correspondant ainsi au pH intérieur des liposomes; (b) incorporation des liposomes à un milieu d'essai aqueux ayant un pH d'au moins environ 0,5 pH unités supérieur au pH intérieur des liposomes, un gradient de pH existant entre le milieu d'essai et l'intérieur des liposomes; (c) incorporation d'un pigment fluorescent au milieu d'essai, le pigment ayant tendance à pénétrer dans les liposomes en raison du gradient de pH et étant sensible au pH de sorte que la fluorescence du pigment soit éliminée à l'intérieur des liposomes; (d) incorporation du composé d'essai au milieu d'essai; si le composé d'essai interrompt la structure des liposomes ou induit la dissipation du gradient de pH entre le milieu d'essai et l'intérieur des liposomes, la fluorescence du pigment n'est pas éliminée; (e) détermination de la fluorescence du milieu d'essai et comparaison avec celle des témoins.

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